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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids
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Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids

机译：在暴露于类固醇的个体患者中，在鼻息肉中的人体调节性T细胞的选择性扩张，而不是相邻的组织显微环境

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Abstract Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (T reg ) cells. T reg cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of T reg cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1 week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. T reg cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced T reg migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of T reg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically T reg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy. Highlights ? Definitive proof of T reg expansion through serial patient NP biopsy and GC therapy ? Unique chemokines may regulate NP recruitment of T reg cells in the presence of GCs. ? Ex vivo migration assay to GC-treated NPs complements in vivo immune changes. ? Titratable immunologic shifts from corticosteroids in chronic upper airway disease
机译：摘要慢性鼻窦炎（CRS），常见的上气道炎症障碍的严重形式与鼻息肉（NPS）有关。 NP疾病通过糖皮质激素（GC）治疗而改善，其细胞效应明显不知。因此，我们评估了GC疗法对CRS患者NPS的影响，重点是调节性T（T reg）细胞。通过来自GC处理的CRS患者和对照的NPS和对照组织中的流式细胞术分析T reg细胞群。在GC暴露后，在NPS内观察到T Reg细胞的选择性膨胀，而不是血液或相邻的乙状体组织。为了确认直接GC效果，在同一患者的NPS在口服GC暴露的1周之前进行了活检。在GC暴露后的4/4 CRS患者中检测到Tregs进入同一NP床的直接扩展。在这些调节细胞中，将T reg细胞尖峰分为次级至细胞募集的细胞募集。趋化因子基因表达分析鉴定了几种趋化因子，特别是CCL4，在NPS时在GC处理时诱导。使用CCR4小分子拮抗剂的趋化因子受体/配体相互作用的中和再在前体内迁移测定中将T Reg迁移降低到GC处理的NPS。我们的研究结果表明，GCS在治疗NP疾病中的常见用途导致从外周位点募集到NP组织中，这对GCS的抗炎作用至关重要。可以部分地通过在皮质类固醇治疗后诱导的趋化因子受体/配体相互作用部分地赋予机械制版T reg膨胀。强调 ？通过连续患者NP活检和GC疗法促进T reg扩增的明确证明？独特的趋化因子可能调节GCS存在下的NP募集T Reg细胞。还前体内迁移测定对GC治疗的NPS体内免疫变化的补充。还从慢性上气道疾病中皮质类固醇的可滴定免疫移位

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